Four unrelated dogs with brittle bones have been identified, each with distinct abnormalities in type I collagen consistent with osteogenesis imperfecta (OI). Three dogs were severely affected and one had moderate disease. Two dogs had dentigenesis imperfecta. The mode of inheritance appeared to be dominant in three dogs and recessive in one dog. During this project, techniques of protein chemistry and cDNA cloning and sequencing will be performed to test the hypothesis that a different mutation in the COL1A1 or COL1A2 gene is the cause of each variant of canine OI. This work will establish the dog as a model of human OI, and permit experimental analyses of the disease that are not possible in humans.